Photodynamic therapy laser

ABSTRACT

A laser system including: a laser source operable to emit a first laser beam having a first operating wavelength and a second laser beam having a second operating wavelength; a fiber optic cable to guide and homogenize the first and second laser beams; an expander to increase the diameter of the first and second laser beams; a cylinder to guide the first and second laser beams and limit respective diameters of the first and second laser beams, wherein the cylinder is positioned after the expander on an optical path of the laser beam; a first optical system to collimate the first and second laser beams, wherein the optical system is positioned after the cylinder on the optical path of the first and second laser beams; a spot-size selector comprising a plurality of apertures, wherein the spot-size selector is positioned after the first optical system on the optical path of the first and second laser beams; and a second optical system to focus the first and second laser beams on a tissue of the patient.

FIELD OF THE INVENTION

This invention relates generally to lasers, and more particularly tophotodynamic therapy laser systems which are compact, portable andeasier to use in a treatment facility.

BACKGROUND

Photodynamic therapy (PDT) is a non-invasive medical procedure used forthe treatment of various diseases. PDT involves the administration of aphotosensitizing compound that concentrates around a portion of tissue.Thereafter the tissue that is concentrated with the photosensitizingcompound is irradiated. The target tissue containing a sufficiently highconcentration of the photosensitizing compound selectively absorbs thelight which induces impairment or destruction of the immediatelysurrounding cells.

One disease treated with PDT is wet age-related macular degeneration.Age-related macular degeneration results in the loss of vision in themacula due to damage in the retina. The wet (or excudative) form ofage-related macular degeneration occurs when blood vessels spread fromthe choroid behind the retina. This abnormal blood vessel growth cancause detachment of the retina. The detachment of the retina can beavoided by preventing the spread of abnormal blood vessel growth. Thespread is prevented by irradiating a photosensitizing compound in atissue that causes impairment or destruction of the surrounding cellsthrough a cytotoxic effect. A method of PDT is described in U.S. Pat.No. 5,756,541, the entirety of which is incorporated by reference.

Typically, photosensitizing agents such as Visudyne® are used to treatthe wet form of age-related macular degeneration. Visudyne® is discussedin U.S. Pat. Nos. 5,171,749, 5,095,030, 5,707,608, 5,770,619, 5,798,349,and 6,074,666, the entireties of which are incorporated by reference.Visudyne® is administered intravenously for approximately ten minutes.After approximately fifteen minutes, the treatment site is activatedwith laser light having a wavelength of approximately 689 nm at 150-600mW/m². As known to those skilled in the art, verteporfin is the genericform or equivalent of Visudyne

There are several laser systems in the prior art to deliver laser lightsuch as Lumenis' Opal Photactivator laser console and modified LumenisLaserLink adapter manufactured by Lumenis, Inc., Zeiss' VISULAS 690slaser and VISULINK® PDT adapter manufactured by Carl Zeiss Meditec Inc.,and Quantel's Activis laser console and ZSL30 ACT™, ZSL120 ACT™,Ceralas™ I laser system and Ceralink™ Slit Lamp Adaptor manufactured byBiolitec, Inc. and HSBMBQ ACT™ slit lamp adapters distributed by QuantelMedical. These prior art laser systems have bulky control panels and areexpensive and increase the costs of PDT for wet age-related maculardegeneration.

Therefore, there is a need in the art for a PDT laser system to be usedfor treating wet age-related macular degeneration, central serouschorioretinopathy (CSC) or polypoidal chorodial vasculopathy (PCV),(subfoveal occult or classical) coroidal neovasculization (CNV), andother similar diseases which is compact, portable, easier to use in atreatment facility, and economical to manufacture.

SUMMARY OF THE INVENTION

The presently disclosed embodiments are directed to solving issuesrelating to one or more of the problems presented in the prior art, aswell as providing additional features that will become readily apparentby reference to exemplary embodiments in the following detaileddescription when taken in conjunction with the accompanying drawings.

According to one embodiment, a treatment beam and an aiming beam isgenerated from a single laser head. The beams are transmitted through afiber optic cable which provides mode-mixing for spot uniformity. Thelaser light is then expanded and collimated. The collimated laser lightis propagated through an aperture wheel that is configured to set a spotsize. The light from the aperture wheel is propagated through a lenswherein it is focused from the lens onto a partially reflective mirror.The partially reflective mirror is configured to reflect a highpercentage of the treatment beam and partially reflect a smallerpercentage of the aiming beam into a patient's eye.

In a further embodiment, light from the partially reflective mirror ispropagated to the treatment site wherein the light beam that irradiatesthe treatment site has a top hat profile of fluence for each desiredspot size.

In a further embodiment, the laser head is designed to run at a higherpower output but actually run at a lower power output to generate lessheat.

In a further embodiment, a tonometer post allows the optical system tobe removably attachable to a slit lamp microscope.

In a further embodiment, heat from the laser head is dissipated in aheat sink. In a further embodiment, the heat sink is coupled to a finarray. The fin array may be coupled to the heat sink with a heat pipe.

In one embodiment, the invention provides a laser system configured foradministering therapy to a patient. The laser system includes: a lasersource operable to emit a first laser beam having a first operatingwavelength and a second laser beam having a second operating wavelength;a fiber optic cable to guide and homogenize the first and second laserbeams; an expander to increase the diameter of the first and secondlaser beams; a cylinder to guide the first and second laser beams andlimit respective diameters of the first and second laser beams, whereinthe cylinder is positioned after the expander on an optical path of thelaser beam; a first optical system to collimate the first and secondlaser beams, wherein the optical system is positioned after the cylinderon the optical path of the first and second laser beams; a spot-sizeselector comprising a plurality of apertures, wherein the spot-sizeselector is positioned after the first optical system on the opticalpath of the first and second laser beams; a second optical system tofocus the first and second laser beams on a tissue of the patient,wherein the second optical system is positioned after the spot-sizeselector on the optical path of the first and second laser beams; and anoptical filter configured to partially reflect the first and secondlaser beams, wherein the optical filter is positioned after the secondoptical system on the optical path of the laser beams, wherein theoptical filter reflects a first percentage of the first laser beam andsecond percentage of the second laser beam, and wherein the firstpercentage is greater than the second percentage.

In another embodiment, a laser system configured for administeringtherapy to a patient, includes: a laser source operable to emit a firstlaser beam operating a first wavelength and a second laser beamoperating at a second wavelength, wherein the laser source operates at1.5 watts or less; a passive cooling system, wherein the passive coolingsystem comprises a heat pipe, a heat sink, and a fin array; a fiberoptic cable coupled to the laser source and configured to guide andhomogenize the first and second laser beams; a first optical systemcoupled to the fiber optic cable and configured to increase the diameterof and collimate the first and second laser beams; a spot-size selectorcoupled to the first optical system and comprising a plurality ofapertures; and a second optical system coupled to the spot-size selectorand configured to focus the laser beam on an eye tissue of the patient.

In a further embodiment, a laser system configured for administeringtherapy to a patient, includes: a laser source operable to emit a firstlaser beam having a first operating wavelength and a second laser beamhaving a second operating wavelength; a fiber optic cable to guide andhomogenize the first and second laser beams, wherein the fiber opticcable has a diameter of about 350 to 450 microns and a length of about200 to 300 millimeters; a first optical system coupled to the fiberoptic cable and configured to increase the diameter of and collimate thefirst and second laser beams; a spot-size selector coupled to the firstoptical system and comprising a plurality of apertures, wherein thespot-size selector is positioned after the first optical system on theoptical path of the first and second laser beams, and the fiber opticcable is the only fiber optic cable between the laser source and thespot-size selector; and a second optical system coupled to the spot-sizeselector and configured to focus the laser beam on an eye tissue of thepatient.

In another embodiment, a method of activating a photoactive drugadministered to a patient intravenously includes: activating thephotoactive agent with a first laser beam generated by a laserapparatus, the first laser beam having a first wavelength; generating asecond laser beam operating at a second wavelength, wherein the combinedpower levels of both the first and second laser beams are 1.5 watts orless; passively cooling the laser apparatus by coupling a heat sink to alaser source of the laser apparatus; guiding the first and second laserbeams through a fiber optic cable coupled to the laser source, whereinthe fiber optic cable homogenizes the first and second laser beams;collimating the first and second laser beams; adjusting a spot-size ofthe first and second laser beams; and focusing the first and secondlaser beams on an eye tissue of the patient, wherein at least the firstlaser beam activates the photoactive drug within the patient's eyetissue to provide therapy to the patient. In a further embodiment, thephoto activate agent comprises verteporfin.

In yet another embodiment, a laser system configured for activating aphotoactive drug administered to a patient intravenously includes: alaser source operable to emit a first laser beam operating a firstwavelength and a second laser beam operating at a second wavelength,wherein the laser source operates at 1.5 watts or less; a passivecooling system, wherein the passive cooling system comprises a heatpipe, a heat sink, and a fin array; a fiber optic cable coupled to thelaser source and configured to guide and homogenize the first and secondlaser beams; a first optical system coupled to the fiber optic cable andconfigured to increase the diameter of and collimate the first andsecond laser beams; a spot-size selector coupled to the first opticalsystem and comprising a plurality of apertures; and a second opticalsystem coupled to the spot-size selector and configured to focus thefirst and second laser beams on an eye tissue of the patient, wherein atleast the first laser beam activates the photoactive drug within thepatient's eye tissue to provide therapy to the patient. In a furtherembodiment, the photo activate agent comprises verteporfin.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure contains at least one drawing in color format.Copies of this patent or patent application publication with colordrawing(s) may be provided by the Office upon request and payment of thenecessary fee.

Various exemplary embodiments of the invention are described in detailbelow with reference to the following Figures. The drawings are providedfor purposes of illustration only and merely depict exemplaryembodiments of the invention. These drawings are provided to facilitatethe reader's understanding of the invention and should not be consideredlimiting of the breadth, scope, or applicability of the invention. Itshould be noted that for clarity and ease of illustration these drawingsare not necessarily drawn to scale.

FIG. 1 illustrates exemplary components of a compact PDT laser accordingto one embodiment of the invention.

FIG. 2 illustrates an exemplary partially reflective mirror according toone embodiment of the invention.

FIG. 3 illustrates an exemplary reflection profile for a partiallyreflective mirror according to one embodiment of the invention.

FIG. 4 illustrates an exemplary top hat output profile for a PDT laseraccording to one embodiment of the invention.

FIG. 5 illustrates the fully assembled internal components of anexemplary PDT laser according to one embodiment of the invention.

FIG. 6 illustrates a modular view of an exemplary low-cost PDT laseraccording to one embodiment of the invention.

FIGS. 7( a)-(b) illustrate an exemplary PDT laser having a housingaccording to one embodiment of the invention.

FIG. 8 illustrates an exemplary PDT laser having a portion of thehousing made transparent for illustrative purposes according to anembodiment of the invention.

FIG. 9 illustrates an exemplary beam splitting system to providecoincident treatment and aiming lasers according to an embodiment of theinvention.

FIG. 10 illustrates an exemplary split fiber system to providecoincident treatment and aiming lasers according to an embodiment of theinvention.

FIG. 11 illustrates an exemplary laser bar system to provide coincidenttreatment and aiming laser beams according to an embodiment of theinvention.

FIG. 12 illustrates an exemplary user interface that enables an operatorto setup a laser and perform therapy therewith.

FIGS. 13 and 14 illustrate some exemplary combinations of aperture size,spot size, and system magnification, in accordance with one embodimentof the invention.

FIG. 15 illustrates an exemplary process flow carried out by software orother circuitry to execute steps for performing a laser-based therapytreatment, such as the treatments described herein.

FIGS. 16( a) and 16(b) illustrate an exemplary PDT laser according to anembodiment of the invention, mounted on a slit lamp, with a mannequin'shead at the position of the patient's head.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The following description is presented to enable a person of ordinaryskill in the art to make and use the invention. Descriptions of specificdevices, techniques, and applications are provided only as examples.Various modifications to the examples described herein will be readilyapparent to those of ordinary skill in the art, and the generalprinciples defined herein may be applied to other examples andapplications without departing from the spirit and scope of theinvention. Thus, the present invention is not intended to be limited tothe examples described herein and shown, but is to be accorded the scopeconsistent with the claims.

The word “exemplary” is used herein to mean “serving as an example orillustration.” Any aspect or design described herein as “exemplary” isnot necessarily to be construed as preferred or advantageous over otheraspects or designs.

Reference will now be made in detail to aspects of the subjecttechnology, examples of which are illustrated in the accompanyingdrawings and tables, wherein like reference numerals refer to likeelements throughout.

It should be understood that the specific order or hierarchy of steps inthe processes disclosed herein is an example of exemplary approaches.Based upon design preferences, it is understood that the specific orderor hierarchy of steps in the processes may be rearranged while remainingwithin the scope of the present invention. The accompanying methodclaims present elements of the various steps in a sample order, and arenot meant to be limited to the specific order or hierarchy presented.

FIG. 1 illustrates an exploded view of an exemplary PDT laser system 100wherein each individual component is shown disconnected from the otherindividual components. Laser light is generated from the laser head 102.The laser head may be obtained commercially (e.g., nLIGHT Pearl™) or maybe constructed of any number of laser generation components (e.g., pumpdiodes, gas lasers). It is understood that any laser design capable ofproviding two or more coincident beams may be utilized.

The laser head 102 generates a treatment and an aiming beam. Accordingto an exemplary embodiment, the treatment beam has a spot size that isvariable from 350 μm to 5000 μm. According to an exemplary embodiment,the laser head 102 can generate fluence rates of 150 mW/cm², 300 mW/cm²,450 mW/cm², and 600 mW/cm². In further embodiments, contact lensmagnification is accounted for when calculating the required fluencerate. In some embodiments, 90% of the treatment beam output power is inthe spectral range of 689 nm±3 nm in order to effectively activate aphotosynthesizing agent (e.g., Visudyne®). The aiming beam may have aspectral output in the range of 635 nm±10 nm. It should be understoodthat the invention is not limited to the spot sizes, fluence rates andtreatment beam ranges disclosed, and the parameters listed above are forexemplary purposes only.

According to an exemplary embodiment, the circularity (the normalizedratio of the minor to the major axis of an ellipse fitted to the beamoutput) is greater than 0.870 for all spot sizes. According to a furtherexemplary embodiment, the beam shall have uniform power distributionthroughout.

According to one embodiment, the uniformity sigma is no greater than 20%when defined as the standard deviation of the intensity of the beamimage calculated by:

$\sigma = \sqrt{\frac{{\Sigma \left( {P_{j} - M} \right)}^{2}}{N - 1}}$

where P is the pixel value, M is the mean pixel value and N is the totalnumber of pixels inside the analysis area. According to one embodiment,the beam profile does not deviate from the equation above duringtreatment.

According to an exemplary embodiment, the laser head 102 provides alight dose of 12.5 J/cm², 25 J/cm², 37.5 J/cm², or 50 J/cm². Theexposure duration can be automatically controlled to deliver a requestedlight dose at a requested fluence. When the requested dose of light hasbeen delivered, the laser head 102 will automatically shut off.

According to an exemplary embodiment, the diameter and position of theaiming beam is coincident with the treatment beam so that a health careprofessional can adequately apply the treatment beam to the treatmentspot. The output power of the aiming beam is 1 mW or less. According toa further embodiment, the visibility of the aiming beam is adjustable(e.g., from barely visible to maximum visibility). In an exemplaryembodiment, the wavelength of the aiming beam is in the range of 625-645nm.

Unlike prior conventional laser systems, the current invention combinesa treatment beam and aiming beam in a single laser head 102, wherebythese embodiments of the present invention advantageously allow thelaser head 102 to be mounted on a typical optical system rather than asa stand-alone console as provided by conventional laser systems. Afurther benefit to combining the treatment and aiming beam is a morecompact PDT laser system 100, which can be more compact, economical tomanufacture, as well as more portable and useable in a treatmentfacility.

According to an exemplary embodiment, the laser head 102 may be currentcontrolled. A current controlled laser head 102 may be manufacturedinexpensively and by controlling the maximum current to the laser,safety is improved. In one embodiment, the laser head 102 may beengineered to operate at a higher power (e.g., 5 W) wherein it isactually run at a lower power (e.g., 1 W or 1.5 W) to reduce heat outputand extend useful life.

It is understood that any method of current control may be utilized. Forexample, current may be controlled by an external foot pedal, a knob, acomputer, or any other device known in the art. It is understood that acurrent control device may be located on the laser head 102. Further, itis understood that the laser head 102 may be voltage controlled (e.g.,voltage corresponding to beam intensity) or controlled by digitalcommunication signals.

According to an exemplary embodiment, the laser head 102 can be made torun below specification at 1 to 1.5 W to generate less heat. In oneembodiment, the laser head 102 is configured to run at a power level ofapproximately 325 mW to 750 mW to further reduce heat generation. Thelower heat generated allows the laser head 102 to be passively cooled.According to an exemplary embodiment, a heat sink 108 is coupled to thelaser head 102. The heat sink 108 is coupled to a heat pipe 106 thattransfers heat to a fin array 104. The fin array 104 dissipates the heatinto the air. The heat sink 108, heat pipe 106, and fin array 104 may bemade of any material known in the art to disperse the heat.

According to one embodiment, the cooling system may utilize workingfluid as known in the field of heat transfer in order cool the laserhead 102. For example, the heat sink 108, the heat pipe 106, and/or thefin array 104 may be filled with a small quantity of working fluid(e.g., water, acetone, nitrogen, methanol, ammonia, or sodium, etc.).Heat is absorbed by vaporizing the working fluid. The vapor transportsheat to the condenser region where the condensed vapor releases heat toa cooling medium. The condensed working fluid is returned to theevaporator by gravity, or by a wick structure on the heat pipe 106 orfin array 104, creating capillary action.

The passive cooling system contributes to reducing the cost of theexemplary PDT laser in a number of ways. First, the passive coolingsystem is less expensive than active cooling systems of the prior art.The passive cooling system cost less to manufacture, to maintain, and tooperate when compared to active cooling systems. Second, the passivecooling system is more compact than active systems, allowing the coolingsystem to be installed in a housing with the laser, and the housingpositioned on known slit lamp microscopes. According to an exemplaryembodiment, the heat sink 108 can assist the laser head 102 to keepingthe therapeutic wavelength within ±1 nm and the therapeutic energywithin 3% of the desired treatment fluence.

According to one embodiment, the laser head 102 has a heat dissipationarea of approximately 11.4 cm by 2.86 cm. Therefore, by having ten timesor more surface area for heat dissipation could allow the laser head 102to operate within therapeutic parameters. According to one embodiment, ametal sheet housing may be utilized to dissipate heat of the laser head102.

According to one embodiment, the heat sink 108, the heat pipe 106, andthe fin array 104 provide approximately a 25 times factor increase insurface area for heat dissipation. According to one embodiment, the heatpipe 106 may be utilized to deliver heat to the fin array 104 that canbe placed at any convenient location within the instrument enclosure.According to an embodiment, the 32.6 cm² heat dissipation surface of thelaser head 102 is attached to a heat sink 108 in combination with a heatpipe 106 and a fin array 104 wherein the heat distribution structure hasa 810 cm² heat dissipation surface. According to one embodiment, thelaser head 102 may be optimally placed near the optical components andthe heat may be transferred to a convenient location on or outside ofthe PDT laser system.

According to an exemplary embodiment, the two laser beams from the laserhead 102 are propagated through a fiber optic cable 110. The fiber opticcable 110 has a curve in the Z-axis. This Z-axis curve works as amode-scrambler. Mode scrambling distributes the optical power in a fiberamong all the guided modes. One known scrambling technique is to splicea length of graded-index fiber between two pieces of step-index, butsuch techniques are expensive and add the complication of fiberalignment. In one embodiment of the present invention, curving the fiberin the Z-axis reduces cost and eliminates the complications of fiberalignment. Further, short fiber optic cable (250 mm, for example) causesrapid coupling between all fiber modes and attenuation of high ordermodes. The fiber optic cable 110 outputs a uniform output intensityprofile and circularity independent of the intensity profile of thelaser head 102.

According to an exemplary embodiment, the fiber optic cable 110 is about250 mm in length and has a diameter of about 400 microns. Given thesmaller size of the fiber optic cable 110, it may be positioned on theoptical system. Typically, prior art systems had long fiber optic cablesconnecting a laser head to the slit lamp optical system. Prior artsystems suffer from degradation of the fiber optic cable and breakage.Thus, the shorter fiber optic cable 110 of embodiments of the presentinvention is more robust and more cost efficient.

The uniform light from the fiber optic cable 110 is propagated to alaser beam expander 112 that expands the output light. In oneembodiment, the fiber optic cable 110 may connect to a fiber lens (notshown) having 4.5 mm focal length (FL). The expanded light is outputtedfrom the laser beam expander 112 into the light diverger 114 thatdiverges the light. According to one embodiment, the beam expander 112may have a lens having a 48 mm FL. In one embodiment, the beam expander112 comprises a biconcave lens having negative power. A diverging beampropagates the length of the beam expander 112 tube, which providesadditional beam divergence to the beam.

The diverged light propagates from the diverger 114 to the collimator116. The light that is outputted from the collimator 116 is moreparallel, relative to the inputted light, in a specific direction andits spatial cross section is smaller. Further, the light exiting thecollimator has a substantially uniform fluence. The light is collimatedso it may pass through a mechanical device and still provide uniformfluence on the target site.

The fiber optic cable 110, the expander 112, the diverger 114, and thecollimator 116 are provided as exemplary embodiments. It is understoodthat alternative mechanisms in the art or additional components may beutilized to deliver light of a uniform fluence.

The light from the collimator 116 is propagated to the aperture wheel118. The aperture wheel 118 comprises a series of apertures to setdifferent spot sizes for the treatment beam. The spot sizes may bephysically set by a person manually rotating the aperture wheel to thedesired spot size. In other embodiments, a motorized system may rotatethe wheel after a desired spot size is selected by a user or a computersystem. It is envisioned that a plurality of different spot size valuesmay be utilized on the aperture wheel 118. Because the light has beencollimated by the collimator 116, the light entering and leaving anaperture in the aperture wheel 118 has a small spatial cross section.According to one embodiment, the aperture wheel 118 is configured toprovide beam diameters of 1.22 mm to 5.5 mm, in twelve approximatelyequal steps. In some embodiments, these beam diameters translate to spotsizes of 1.0 mm to 6.4 mm, when appropriate contact lenses are used.According to one embodiment, one spot of 500 microns is delivered by theaperture wheel 118 for the treatment of polypoidal choroidalvasculopathy and a range of spots from 1000 to 6400 microns with anaverage step increment of approximately 400 microns is delivered forPDT. According to one embodiment, the PDT laser provides laser spotsizes smaller than 1 mm for CSC, PCV, CNV, age-related maculardegeneration (AMD) or similar indications.

Rather than using one or more lenses to set a spot size, in oneembodiment of the invention a single aperture wheel 118 is utilized.This provides costs savings as a metal wheel can be manufactured cheaperthan a lens or a zoom system. In addition, aperture wheel 118 is moredurable than a lens system and less likely to degrade or becomemisaligned over time. Further, the aperture wheel 118 is easilyinterchangeable or replaceable with other aperture wheels. For example,a new series of spot sizes may be utilized by cheaply replacing theaperture wheel 118 having a set of spot size values to another aperturewheel having a different set of spot size values.

According to exemplary embodiments of the invention, the aperture wheel118 can be configured to provide spot sizes of 500-6000 microns.

Light passes through the aperture wheel 118 to a lens assembly 120. Inone embodiment, the lens assembly 120 focuses the image of the aperturewheel 118 to have a 1:1 input/output ratio and projects light to apartially reflective mirror 122. According to one embodiment, the lensassembly 120 comprises two lenses (120 a and 120 b). The first lens 120a may have a 56 mm focal length (FL) and the second lens 120 b may havea 48 mm FL. According to another embodiment, both lenses of the lensassembly 120 may have a 50 mm FL.

FIG. 2 illustrates an aiming beam 124 propagated onto an exemplarypartially reflective mirror 122 from the lens assembly 120 (FIG. 1).Approximately 50% of the aiming beam 124 is reflected by the partiallyreflective mirror 122 to the patient's eye 126. Approximately 50% of theaiming beam passes through and is not reflected by the partiallyreflective mirror 122.

The partially reflected light beam 128 illuminates a target site 130 ofthe patient's eye 126. A portion of the reflected beam 128 is reflectedoff the target site 130. Approximately 50% of the light that isreflected off of the target site 130 is again reflected by the partiallyreflected mirror 122. The other 50% of light reflected off of the targetsite 130 is transmitted through the partially reflective mirror 122 tothe optics of the slit lamp and ultimately to the clinician's eyes. Thisenables the clinician to see the target site 130 of the patient's eye126. In some embodiments, the total light emission striking thephysician's eye does not exceed safe limits as defined by the AmericanNational Standard for Safe Use of Lasers (ANSI Z136), the disclosure ofwhich is herein incorporated by reference in its entirety. ANSI Z136provides safe laser exposure limits for general use. If the laserexposure is below the limits defined by the standard there should be nothermal damage to the retinal tissues due to laser exposure alone.

The partially reflective mirror 122 can act similarly to reflect thetreatment beam. For example, the partially reflective mirror 122 can beconfigured to reflect 90% of the treatment beam. The reflected treatmentbeam would propagate onto the eye 126 and only a small portion of thatbeam would be reflected back to the partially reflected mirror 122. 10%of the light from the tissue reflected light would be propagated to theclinician's eyes. The small percentage of the treatment beam ultimatelypropagated to the clinician's eyes would not be harmful. In someembodiments, the total light emission striking the physician's eye doesnot exceed safe limits as defined by ANSI Z136, the disclosure of whichis herein incorporated by reference in its entirety.

FIG. 3 illustrates an exemplary reflective profile for the partiallyreflective mirror 122. According to an exemplary embodiment, a treatmentbeam has a wavelength of 689 nm and an aiming beam has a wavelength of635 nm. Here, the partially reflective mirror 122 would reflect 90% ofthe treatment beam and 50% of the aiming beam. These figures areexemplary. It is understood that a partially reflective mirror 122 mayhave any alternative desired reflective profiles.

The treatment and aiming light ultimately propagated from the partiallyreflective mirror 122 to the eye 126 has a top hat beam. A top hat beamis understood in the art and is a laser beam that has a near uniformfluence within a circular disk. FIG. 4 illustrates an exemplary top hatprofile for a spot size of 4600 microns for the X and the Y plane thatis propagated onto the eye 126. In some embodiments, the PDT laser has amaximum total power of 200 mW for the largest spot size of the laser.However, it is understood that any spot size may be selected to bepropagated at any desired power density depending on the desiredapplication. It is further understood that the top hat profile may beoptimized for more uniform distribution.

Returning to the exemplary embodiment of FIG. 1, the tonometer post 134may be used to attach the PDT laser system 100 to a conventional slitlamp microscope. According to one embodiment, the tonometer post 134 isdesigned to couple to a Haag-Strait or equivalent slit lamp microscope.It is understood that the tonometer post 134 is exemplary and that anequivalent attachment mechanism may be provided to attach the PDT Lasersystem 100 to a slit lamp microscope or other similar ophthalmic device.

According to an exemplary embodiment, the PDT laser system 100 ismounted on a slit lamp microscope so that the treatment spot is alignedand focused coincident with the slit illumination of a slit lamp.

It is understood that FIG. 1 is provided as an exemplary embodiment andthat other components may be added. For example, it is understood thatthe PDT laser system 100 may be constructed as a stand-alone PDT devicewith proper casings, removably attachable to a slit lamp microscope, orpermanently attached to a slit lamp microscope.

FIG. 5 illustrates the fully assembled internal components of PDT laser200 having a laser head 202, a heat sink 204, a heat pipe 206, a finarray 208, a fiber optic cable 210, an expander 212, a diverger 214, acollimator (not shown), an aperture wheel 218, a lens assembly 220, apartially reflective mirror 222, and a tonometer post 234. In someembodiments, PDT laser 200 comprises the elements of PDT laser 100discussed above with respect to FIG. 1.

FIG. 6 illustrates a modular block diagram of exemplary PDT laser inaccordance with an embodiment of the invention. PDT laser housing 336houses a laser head 302. The laser head 302 generates coherent lighthaving a narrow bandwidth of +/−3 mm, a central wavelength of 689 nm,and light that supports a fluence rate of 0 to 600 mW/cm² light plus acollinear aiming beam. The light from the laser head 302 is provided tothe mode scrambler 338. The mode scrambler 338 may be a fiber opticcable or any mode scrambler known in the art. According to oneembodiment, the optical modes that occur when a laser beam istransmitted by a multi-mode fiber optic are scrambled in the modescrambler 338 to generate a circular beam with a top hat intensityprofile. According to one embodiment, the laser head 302 may be a laserdiode that combines the laser treatment beam and the aiming beam so thattheir laser outputs are optically collinear with regard to the modescrambler 338.

The light output 340 from the mode scrambler 338 has a top hat intensityprofile that propagates to the beam expander/telescope/collimator 342.According to one embodiment, the top hat intensity profile is desirablebecause it provides a very uniform optical fluence rate (mW/cm²) acrossthe laser beam cross-sectional area to provide uniform activation of aphotosensitizer across the area of tissue being treated.

According to one embodiment, the laser beam from the mode scrambler 338is expanded from 400 microns to 12 mm in diameter. The collimated lightfrom the expander/telescope/collimator 342 pass collimated light havinga 12 mm diameter to the spot size selector 344.

According to one embodiment, the spot size selector 344 may be machinedwith a plurality of spot size holes. The spot size selector 344 may bemanually rotated so that one spot size is selected at a time. When thespot size is selected, the hole intersects with the expanded laser beamand the laser light is transmitted through the hole onto projectionoptics 346. According to one embodiment, spot sizes in the range of 1.0mm to 6.4 mm may be produced on the retina to treat lesion diametersfrom 0 to 5.4 mm. It is understood that a varying range of spot sizesmay be used as known in the art.

The light passes through the spot size selector 344 to the projectionoptics 346 wherein the projection optics provide a magnification factor(M) of 0.78. It is understood that a varying range of M may be used asknown in the art. The light is projected from the projection optics 346to the eye 348 to excite a photosensitizing agent.

FIG. 7( a) illustrates an exemplary PDT laser system 400 having ahousing 436 and a tonometer post 434. The housing 436 has a display 450that can display various treatment and laser parameters. According toone embodiment, the display 450 shows the therapeutic count down time:83 seconds to 0. FIG. 7( b) illustrates a profile view of an exemplaryembodiment of the PDT laser system 400.

FIG. 8 illustrates a side view of an exemplary PDT laser system 500,with the housing made transparent for illustrative purposes. A tonometerpost 534 is provided on the outside of the housing 536. Inside thehousing 536, a laser head 502 generates a treatment and an aiming beamthat is propagated through a fiber optic cable 510. The fiber opticcable 510 scrambles the modes. A beam expander/telescope/collimator 542expands and collimates the light. An aperture wheel 518 selects anaperture size from the light from the expander/telescope/collimator 542.The light from the aperture wheel 518 is propagated through a lensassembly (not shown) onto the partially reflected mirror to an eye (notshown). Heat is dissipated from the laser head 502 through the heat sink504, heat pipe 506, and the fin array 508.

FIGS. 9, 10, and 11 illustrate exemplary optical configurations toprovide a coincident aiming and laser beam. FIG. 9 illustrates a beamsplitter 652 that combines a 689 nm therapy laser 654 and an aiminglaser 656 to a tissue target 658. FIG. 10 illustrates a 689 nm therapylaser 754 and an aiming laser 756 that are combined in a split fiber760. The split fiber 760 delivers the two beams to an optical system 762having four lenses that propagates the light to the tissue target 758.FIG. 11 illustrates a laser head 802 that generates a 689 nm therapylaser 854 and an aiming laser 856 that is propagated through a fiberoptic cable to a tissue target 858. It is understood that the therapy oraiming laser beams (654, 754, and 854) described herein may be of anydesired wavelength as known in the art.

It is understood that the optical system 762 may be configured asdescribed in previous embodiments or in any other method known in theart. It is further understood that the optical system 762 may have anynumber of lenses. It is understood that the systems and methodsdescribed herein to provide coincident aiming and treatment beams aremerely exemplary and that any method known in the art may be utilized toprovide coincident treatment and aiming beams.

FIG. 12 illustrates an exemplary user interface 900 that enables anoperator—such as a physician, an ophthalmologist, a clinician, etc.—tosetup a laser and perform therapy therewith, such as the lasersdescribed herein. User interface 900 includes a display 902, a contactlens selector 904, a fluence rate selector 906, an aiming beam intensityselector 908, an emergency stop 910, a laser state selector 912, a spotsize selector 914, and a key switch 916.

In some embodiments, display 902 is a two digit display that displays atreatment countdown, provides feedback when the fluence rate is changedand displays error codes when required. The display may provide acountdown from 83 seconds when the laser is fired and, in someembodiments, the countdown cannot be altered except by restarting thelaser system.

Contact lens selector 904 may provide for toggling between availablecontact lens magnifications. For example, contact lens selector 904 maytoggle between a 1.06× contact lens magnification (corresponding to aVolk Area Centralis contact lens or equivalent) and a 1.47× contact lensmagnification (corresponding to a Mainster Wide Field contact lens orequivalent). FIGS. 13 and 14 illustrate some exemplary combinations ofaperture size, spot size, and system magnification, in accordance withone embodiment of the invention. It will be understood by one ofordinary skill in the art that other combinations of spot sizes, systemmagnification, and apertures sizes could be equivalently used withoutdeviating from the scope of the invention.

According to one embodiment, fluence rate selector 906 allows thephysician to select the desired fluence rate. When pressed while thelaser is in setup mode, this button cycles the system through fluencerates of 600, 450, 300 or 150 mW/cm². When the fluence rate is changed,the display will read 60, 45, 30 or 15, signifying 600, 450, 300 or 150mW/cm². When a 600 mW/cm² is selected as the fluence rate, a green LEDshows beside the fluence rate selector. When a fluence rate other than600 mW/cm² is selected as the fluence rate, a red LED shows beside thefluence rate selector. It is to be understood that the settings of thefluence rate selector 906 and corresponding display of LEDs may bevaried without deviating from the scope of the invention.

In some embodiments, aiming beam intensity selector 908 allows forcontinuous adjustment of the aiming beam from a minimum of 0 mW to amaximum of <1 mW output.

According to one embodiment, emergency stop 910 is a latching switchthat will immediately disable power to the entire unit. A restart of thesystem will occur when the switch is “unlatched” and it will return todefault settings.

Laser state selector 912 may be adjusted to one of a ready state or astand-by state. In both states the aiming beam is on. However, only inthe ready state can the treatment beam be activated. When the laser isin “ready” mode a green LED shows beside the laser state selector. Whenthe laser is in “standby” mode a red LED shows beside the laser stateselector.

According to one embodiment, spot size selector 914 is rotated to selectthe laser beam spot size.

Key switch 916 may be a main power switch. When this key switch isturned to the “on” position, the laser powers up and the aiming beam isenabled. Whenever the key is turned on, the system defaults to standardparameters of 600 mW/cm², 83 second treatment timing, and 1.06× contactlens magnification. If required, the key can be removed from the switchwhen the system is in the “off” mode providing a simple way to controlaccess to the laser system.

Although not illustrated in FIG. 12, the laser system may include othercomponents, such as a foot switch and other controls and indicators. Afoot switch may activate the treatment beam when the laser is in “ready”mode. If the foot switch is released, the treatment beam is deactivated.If the treatment beam is interrupted during use by releasing the footswitch, the 83 second countdown will stop. If the foot switch isactivated again without first shutting down the laser system, thecountdown will resume from where it left off. Other controls may includea remote interlock connector that prevents operation of the treatmentbeam when the terminals of the connector are not electrically joined andan audible signal to indicate that the treatment beam is being fired.

FIG. 15 illustrates an exemplary process flow 1000 carried out bysoftware or other circuitry to execute steps for performing alaser-based therapy treatment, such as the treatments described herein.Process flow 1000 includes a therapy mode process 1002, a laserenergized process 1004, a standby mode process 1006, a set defaultparameters process 1008, an aiming laser process 1010, and a setup modeprocess 1012. Each process in process flow 1000 includes arrowsindicating an event or condition required to exit the process, anunconditional exit from a process, variables, and launches of parallelprocesses.

The following exemplary method of system setup may be performed inconjunction with process flow 1000 above: (1) attach the laser unit tothe slit lamp (SL) and align the SL observation system and illuminationsystem, (2) turn laser unit power on using key switch, (3) allow thelaser unit to self-test for approximately 15 seconds, (4) place thefocusing post in the SL and bring it into focus while looking throughthe SL binoculars and having a narrow slit beam illumination, and (5)adjust the laser unit's lever and focusing knob, to ensure that thelaser is aligned and focused at the same location as the slit beam.

The following exemplary method of system standby may be performed inconjunction with process flow 1000 above: (1) power-up laser and laserdefaults to a standard treatment using 600 mW/cm² 83 second timing and a1.06× contact lens, (2) if a standard treatment is desired, followstandard treatment method (see below), (3) if a non-standard treatmentis desired: (3a) depress and hold the bottom button (see FIG. 12) untilthe green led flashes, the display will indicate ‘00’ and (3b) using theupper button (see FIG. 12), alternate fluence rates may be selected(either 600, 450, 300 or 150 mW/cm²—pressing the button will cycle thefluence rates through the available options and the display willindicate 60, 45, 30 or 15 signifying 600, 450, 300 or 150 mW/cm².)

The following exemplary method of standard treatment method may beperformed in conjunction with process flow 1000 above: (1) place thelaser in ready mode by pressing the upper button (see FIG. 12), (2)adjust the intensity of the aiming beam as desired, (3) adjust the spotsize (if spot sizes larger than 4.5 mm are required, change the contactlens magnification factor to 1.47×), (4) activate the laser (forexample, using a foot pedal), (5) keep foot pedal pressed (counter willrun from 83 seconds and at 0 an audible beep will sound, at which timeboth the aiming and treatment beams will be shutdown).

In some embodiments, additional safety measures may be added. In someembodiments, a latching emergency stop switch can immediately disablepower to the entire unit. In one embodiment, the control unit monitorsthe therapeutic laser during activation, ensuring that the wavelengthand power levels remain within the set parameters during treatment. Inother embodiments, a watchdog feature ensures that, in case of failureof the control unit, the system will be shut down. According to oneembodiment, maximum output of the laser is set in the circuit design,preventing excessive laser output in the case of simultaneous controlunit and watchdog failure. In some embodiments, a door interlock isprovided that prevents use of the treatment beam if the operating roomdoor is opened.

In some embodiments, a bar code scanner is added to a laser system toallow clinicians to quickly setup the system to correspond to thetreatment parameters of one or more photoactivating drugs. For example,a vial of a photoactive drug (such as Visudyne®, for example) may beequipped with a bar code identifying the drug within the vial. In oneembodiment, the bar coding system incorporates a radio frequencyidentification system (“RFID”) that gathers information from a RFID tagon the vial. In some embodiments, the laser system may be preprogrammedwith the identified photoactive drug's treatment parameters. In thoseembodiments, simply identifying the drug may be sufficient. In otherembodiments, the bar code or RFID tag may include other information suchas the exact treatment parameters, expiration date of the drug, etc.Once the treatment parameters of the identified drug are determined, thelaser system may automatically alter the beam wavelength, fluence rate,power, duration of treatment, etc. accordingly. In some embodiments, thelaser system may require additional physical changes to correspond to aparticular photosensitive drug, such as replacing the partiallyreflective mirror. In some embodiments, the bar coding system andassociated circuitry are stored in the laser housing. In someembodiments, the bar coding system may be housed separately. Somefurther embodiments may include an approval system on the laser systemthat requests user confirmation before adjusting the laser systemtreatment parameters. In some embodiments, the laser system isconfigured to read treatment parameters of all PDT compounds. In somefurther embodiments, the bar coding system is configured to readtreatment parameters from one or more of a vial, a box, a referencebook, and a electronic display. Such electronic displays can be a smartphone or a computer or any other electronic display and the informationmay be gathered from an email, a PDT compound manufacturer's website, ora database, for example.

FIGS. 16( a) and 16(b) illustrate an exemplary PDT laser 1102 accordingto an embodiment of the invention, mounted on a slit lamp 1104, with amannequin's head 1106 at the position of the patient's head. PDT laser1102 may comprise any of the PDT laser's described herein. The slit lamp1104 may comprise any slit lamp which has structure to receive exemplaryPDT laser 1102.

The following is a description of an exemplary working example utilizingone or more embodiments of the disclosed invention. Patient I is treatedwith a regimen in which they are administered 6 mg/M² (of body surfacearea) of verteporfin in a commercially available liposomal intravenouscomposition obtainable from QLT PhotoTherapeutics, Vancouver, BC,assignee of the present application. Administration is intravenous.Thirty minutes after the start of infusion, the patient is administereda laser light having a wavelength of about 689 nm at 150-600 mW/m².Patient II is administered 6 mg/M² of verteporfin in the liposomalformulation, intravenously as with Patient I, but the laser light begins20 minutes after the start of infusion. Patient III is subject to aregime identical to Patient I except 12 mg/M² of verteporfin isadministered.

Although individual components have been described herein, it isunderstood that any component known in the art may be used to accomplishthe same or similar function.

It is understood that an ocular lens such as Mainster, Volk AreaCentralis, or any other indirect image lens known in the art may beutilized to aid in PDT or other treatments. These ocular lenses arerequired to focus the laser on the back of the retina. Without theocular lenses the fundus cannot be visualized and the laser beam cannotbe focused to the expected area on the patient's retina. It is furtherunderstood that any indirect (real) image contact lens may be utilizedfor PDT.

It is understood that many unlabeled portions of the figures mayrepresent common mechanical connectors or pieces and are representativeof any mechanical connector or piece known in the art.

It is understood that the invention is not limited to PDT and may beconfigured to be utilized in other photocoagulation or non-thermalprocedures (e.g., transpupillary thermotherapy). It is furtherunderstood that the invention may be utilized for the treatment ofcentral serous chorioretinopathy (CSC) or polypoidal chorodialvasculopathy (PCV), subfoveal occult or classical) coroidalneovasculization (CNV), age-related macular degeneration (AMD). It alsounderstood that principles of embodiments of the invention could beexpanded to include thermal treatments.

While various embodiments of the present invention have been describedabove, it should be understood that they have been presented by way ofexample only, and not of limitation. Likewise, the various diagrams maydepict an example architectural or other configuration for theinvention, which is done to aid in understanding the features andfunctionality that can be included in the invention. The invention isnot restricted to the illustrated example architectures orconfigurations, but can be implemented using a variety of alternativearchitectures and configurations. Additionally, although the inventionis described above in terms of various exemplary embodiments andimplementations, it should be understood that the various features andfunctionality described in one or more of the individual embodiments arenot limited in their applicability to the particular embodiment withwhich they are described, but instead can be applied, alone or in somecombination, to one or more of the other embodiments of the invention,whether or not such embodiments are described and whether or not suchfeatures are presented as being a part of a described embodiment. Thusthe breadth and scope of the present invention should not be limited byany of the above-described exemplary embodiments.

1.-11. (canceled)
 12. A laser system configured for administering therapy to a patient comprising: a laser source operable to emit a first laser beam operating a first wavelength and a second laser beam operating a second wavelength, wherein the laser source operates at 1.5 watts or less; a passive cooling system, wherein the passive cooling system comprises a heat pipe, a heat sink, and a fin array; a fiber optic cable coupled to the laser source and configured to guide and homogenize the first and second laser beams; a first optical system coupled to the fiber optic cable and configured to increase the diameter of and collimate the first and second laser beams; a spot-size selector coupled to the first optical system and comprising a plurality of apertures; and a second optical system coupled to the spot-size selector and configured to focus the first and second laser beams on an eye tissue of the patient.
 13. The laser system of claim 12, further comprising an optical filter configured to partially reflect the first and second laser beams, wherein the optical filter reflects a first percentage of the first laser beam and a second percentage of the second laser beam, the first percentage being greater than the second percentage.
 14. The laser system of claim 13, wherein the laser system is contained within a single housing.
 15. The laser system of claim 14, wherein the housing is configured to be attached to a slit-lamp microscope.
 16. A laser system configured for administering therapy to a patient comprising: a laser source operable to emit a first laser beam having a first operating wavelength and a second laser beam having a second operating wavelength; a fiber optic cable to guide and homogenize the first and second laser beams, wherein the fiber optic cable has a diameter of approximately 350 to 450 microns and a length of approximately 200 to 300 millimeters; a first optical system coupled to the fiber optic cable and configured to increase the diameter of and collimate the first and second laser beams; a spot-size selector coupled to the first optical system and comprising a plurality of apertures, wherein the spot-size selector is positioned after the first optical system on the optical path of the first and second laser beams, and the fiber optic cable is the only fiber optic cable between the laser source and the spot-size selector; and a second optical system coupled to the spot-size selector and configured to focus the first and second laser beams on an eye tissue of the patient.
 17. The laser system of claim 16, further comprising an optical filter configured to partially reflect the laser beam, wherein the optical filter is positioned after the second optical system and reflects a first percentage of the first laser beam and a second percentage of the second laser beam, the first percentage being greater than the second percentage.
 18. The laser system of claim 16, wherein the laser source operates at 1.5 watts or less.
 19. The laser system of claim 18, further comprising a passive cooling system attached to the laser source.
 20. The laser system of claim 19, wherein the passive cooling system comprises a heat pipe, a heat sink, and a fin array.
 21. A method of activating a photoactive drug administered to a patient intravenously, comprising: activating the photoactive agent with a first laser beam generated by a laser apparatus, the first laser beam having a first wavelength; generating a second laser beam operating at a second wavelength, wherein the combined power levels of both the first and second laser beams are 1.5 watts or less; passively cooling the laser apparatus by coupling a heat sink to a laser source of the laser apparatus; guiding the first and second laser beams through a fiber optic cable coupled to the laser source, wherein the fiber optic cable homogenizes the first and second laser beams; collimating the first and second laser beams; adjusting a spot-size of the first and second laser beams; and focusing the first and second laser beams on an eye tissue of the patient; wherein at least the first laser beam activates the photoactive drug within the patient's eye tissue to provide therapy to the patient.
 22. The method of claim 21, wherein the photoactive drug comprises verteporfin.
 23. A laser system configured for activating a photoactive drug administered to a patient intravenously, the system comprising: a laser source operable to emit a first laser beam operating a first wavelength and a second laser beam operating at a second wavelength, wherein the laser source operates at 1.5 watts or less; a passive cooling system, wherein the passive cooling system comprises a heat pipe, a heat sink, and a fin array; a fiber optic cable coupled to the laser source and configured to guide and homogenize the first and second laser beams; a first optical system coupled to the fiber optic cable and configured to increase the diameter of and collimate the first and second laser beams; a spot-size selector coupled to the first optical system and comprising a plurality of apertures; and a second optical system coupled to the spot-size selector and configured to focus the first and second laser beams on an eye tissue of the patient, wherein at least the first laser beam activates the photoactive drug within the patient's eye tissue to provide therapy to the patient.
 24. The system of claim 23, wherein the photoactive drug comprises verteporfin. 